The genetic control of the chromosome cycle in Drosophila melanogaster is being investigated. Mutants isolated by three different criteria--meiotic mutants, mutagen sensitive mutants, and temperature sensitive lethals--have been shown to be rich sources of lesions in the processes required for a normal chromosome cycle. Recombination-defective meiotic mutants have been studied to determine whether these loci also function during somatic cell divisions. Although the 14 recombination-defective meiotic mutants studied drastically reduce meiotic crossing over they do not decrease spontaneous mitotic exchange, suggesting that meiotic and mitotic recombination are under separate control. However, most of these loci do function in mitotic cells since mutants at seven of the eight recombination-defective loci examined showed an increased incidence of mitotic chromosome instability. The immediate causes of instability differ between loci and include chromosome breakage, chromosome loss and mitotic recombination. The nature of the mitotic lesion in these mutants is being further investigated by genetic and cytological techniques. To detect mutants, defective in essential gene functions involved in the chromosome cycle, we have isolated a group of temperature-sensitive lethal mutants that produce mitotic chromosome instability at semi-restrictive temperatures. The nature of the defect in these mutants is being characterized.